In a 13-season career, Wambsganss posted a .259 batting average with seven home runs and 519 run batted in in 1492 games played. Due to his long surname, Wambsganss was often called "Wamby" by headline writers.

Wambsganss was the regular second baseman of the Cleveland Indians for ten years. Over a thirteen-year Major League career, he amassed 4,269 assists with 3,420 putouts and turned 605 double plays. He committed only 375 errors in 8,064 chances for a significant .954 fielding percentage. Batting from the second or eighth spot, Wambsganss averaged 74.2 runs per year from 1919 to 1923. He scored a career-high 89 runs in 1922. He hit a career-high .295 in 1918 and hit .290 in 1923, his last season with Cleveland. He was sent to the Boston Red Sox in the same trade that brought first basemanGeorge Burns to the Indians.

In 1924 with Boston, Wambsganss hit .275 and collected career-highs in hits (174) and runs (93). After a sub-par season in 1925, he was sold to the Philadelphia Athletics. He finished his Major League career with the A's in 1926, batting .352 in 54 games.

In game five of the 1920 World Series played at League Park, Wambsganss caught a fifth-inning line drive batted by Clarence Mitchell, stepped on second base to retire Pete Kilduff, and tagged Otto Miller coming from first base, to complete the first, and to date, only unassisted triple play in World Series history. Earlier in the game, Wambsganss' teammate Elmer Smith hit the first grand slam in World Series history off Brooklyn Robins pitcherBurleigh Grimes, in the first inning with none out. The historic blast scored Charlie Jamieson, Wambsganss, Tris Speaker, and Smith. Brooklyn fell to the Indians in an 8–1 loss. Cleveland winning pitcher Jim Bagby helped himself by hitting a three-run home run in the third. It was the first home run hit by a pitcher in modern World Series history.

After the World Series, Cleveland fans presented Wambsganss with a medal to commemorate the unassisted triple play. The medal was lost the following April while Wambsganss was traveling aboard a train.[2]

After his last year in the Major Leagues, Wambsganss played for Triple-A Kansas City of the American Association. After coaching New Orleans of the Southern League in 1930, he returned to the Kansas City club as manager in 1931.[3]

When interviewed in the 1960s by Lawrence Ritter for the classic oral history The Glory of Their Times, Wambsganss recalled: "Funny thing, I played in the big leagues for 13 years, 1914 through 1926, and the only thing that anybody seems to remember is that once I made an unassisted triple play in a World Series. Many don't even remember the team I was on, or the position I played, or anything. Just Wambsganss-unassisted triple play! You'd think I was born on the day before and died on the day after."

Wambsganss died of heart failure in Lakewood, Ohio on December 10, 1985. He was 91 years old. Wambsganss was buried at Calvary Cemetery in Cleveland.[5]